A comparison of methods for treatment selection in seamless phase II/III clinical trials incorporating information on short-term endpoints

In an adaptive seamless phase II/III clinical trial interim analysis, data are used for treatment selection, enabling resources to be focused on comparison of more effective treatment(s) with a control. In this paper, we compare two methods recently proposed to enable use of short-term endpoint data for decision-making at the interim analysis. The comparison focuses on the power and the probability of correctly identifying the most promising treatment. We show that the choice of method depends on how well short-term data predict the best treatment, which may be measured by the correlation between treatment effects on short- and long-term endpoints.

littleBits go LARGE: making electronics more accessible to people with learning disabilities

The “littleBits go LARGE" project extends littleBits electronic modules, an existing product that is aimed at simplifying electronics for a wide range of audiences. In this project we augment the littleBits modules to make them more accessible to people with learning disabilities. We will demonstrate how we have made the modules easier to handle and manipulate physically, and how we are augmenting the design of the modules to make their functions more obvious and understandable.

Trends in domestic electricity consumption in Botswana

Data on electricity consumption patterns relating to different end uses in domestic houses in Botswana is virtually non-existent, despite the fact that the total electricity consumption patterns are available. This can be attributed to the lack of measured and quantified data and in other instances the lack of modern technology to perform such investigations. This paper presents findings from initial studies that are envisaged to bridge the gap. Electricity consumption patterns of 275 domestic households in Gaborone (the capital city of Botswana) have been studied. This was carried out through a questionnaire survey and electricity measurements. Households were categorized based on the number of people occupying the house. From the study, it was evident that the number of people influences the amount of energy a household use although this cannot be treated as an independent factor when assessing energy use. The study also indicated that heating, cooling and domestic hot water (DHW) account for over 30% of energy used in the home. This is worth considering in energy consumption reduction measures. Due to a small sample size, it would not be wise to draw sweeping conclusions from the analysis of this paper or to make statements that would be aimed at influencing policies. However, the results presented forms a formidable base for further research, which is currently on going.

Formulaic sequences in native and non-native argumentative writing in German

Whereas there is substantial scholarship on formulaic language in L1 and L2 English, there is less research on formulaicity in other languages. The aim of this paper is to contribute to learner corpus research into formulaic language in native and non-native German. To this effect, a corpus of argumentative essays written by advanced British students of German (WHiG) was compared with a corpus of argumentative essays written by German native speakers (Falko-L1). A corpus-driven analysis reveals a larger number of 3-grams in WHiG than in Falko-L1, which suggests that British advanced learners of German are more likely to use formulaic language in argumentative writing than their native-speaker counterparts. Secondly, by classifying the formulaic sequences according to their functions, this study finds that native speakers of German prefer discourse-structuring devices to stance expressions, whilst British advanced learners display the opposite preferences. Thirdly, the results show that learners of German make greater use of macro-discourse-structuring devices and cautious language, whereas native speakers favour micro-discourse structuring devices and tend to use more direct language. This study increases our understanding of formulaic language typical of British advanced learners of German and reveals how diverging cultural paradigms can shape written native speaker and learner output.

Intersections of Jane Jacobs’ conditions for diversity and low-carbon urban systems: a look at four global cities

Countless cities are rapidly developing across the globe, pressing the need for clear urban planning and design recommendations geared towards sustainability. This article examines the intersections of Jane Jacobs’ four conditions for diversity with low-carbon and low-energy use urban systems in four cities around the world: Lyon (France), Chicago (United-States), Kolkata (India), and Singapore (Singapore). After reviewing Jacobs’ four conditions for diversity, we introduce the four cities and describe their historical development context. We then present a framework to study the cities along three dimensions: population and density, infrastructure development/use, and climate and landscape. These cities differ in many respects and their analysis is instructive for many other cities around the globe. Jacobs’ conditions are present in all of them, manifested in different ways and to varying degrees. Overall we find that the adoption of Jacobs' conditions seems to align well with concepts of low-carbon urban systems, with their focus on walkability, transit-oriented design, and more efficient land use (i.e., smaller unit sizes). Transportation sector emissions seems to demonstrate a stronger influence from the presence of Jacobs' conditions, while the link was less pronounced in the building sector. Kolkata, a low-income, developing world city, seems to possess many of Jacobs' conditions, while exhibiting low per capita emissions - maintaining both of these during its economic expansion will take careful consideration. Greenhouse gas mitigation, however, is inherently an in situ problem and the first task must therefore be to gain local knowledge of an area before developing strategies to lower its carbon footprint.

Legal and regulatory barriers to effective public-private partnership governance in Kazakhstan

Purpose – The purpose of this paper is to provide a critical assessment of legal and regulatory impediments to effective governance of public-private partnerships (PPPs) in Kazakhstan. Design/methodology/approach – The qualitative study develops propositions from the PPP literature and then tests them against findings from in-depth interviews. Interviewees have been selected by a purposeful sampling from PPP projects in Kazakhstan as well as from national and regional PPP centres. Findings – The identified barriers to effective PPP management include irregularities in the PPP legal framework, such as lack of legal definition of a PPP and controversy with the government guarantee’s legal status for its long-term payments to partnerships; bureaucratic tariff setting for partnership services; non-existent opportunity for private asset ownership; and excessive government regulation of PPP workers’ wage rates. Practical implications – The partners’ opposing perspectives on a number of PPP issues show that management needs to identify and carefully reconcile stakeholder values in a partnership in order to achieve more effective PPP governance. Practitioners, particularly those in the public agencies, have to be concerned with ways to reduce the government overregulation of the private operators, which is likely to result in greater PPP flexibility in management and, ultimately, higher efficiency in delivering the public services. Originality/value – By elucidating multiple examples of overregulation and PPPs’ inefficiency, the paper demonstrates that the government dominance in PPP management is conceptually inappropriate. Instead, the government should adopt the concept of co-production and manage its relations with the private sector partner in a collaborative fashion.

A review of drought in the Middle East and Southwest Asia

The Middle East and Southwest Asia comprise a region that is water-stressed, societally vulnerable, and prone to severe droughts. Large-scale climate variability, particularly La Niña, appears to play an important role in region-wide drought, including the two most severe of the last fifty years—1999-2001 and 2007-2008—with implications for drought forecasting. Important dynamical factors include orography, thermodynamic influence on vertical motion, storm track changes, and moisture transport. Vegetation in the region is strongly impacted by drought and may provide an important feedback mechanism. In future projections, drying of the eastern Mediterranean is a robust feature, as are temperature increases throughout the region, which will affect evaporation and the timing and intensity of snowmelt. Vegetation feedbacks may become more important in a warming climate. There are a wide range of outstanding issues for understanding, monitoring, and predicting drought in the region, including: dynamics of the regional storm track, the relative importance of the range of dynamical mechanisms related to drought, regional coherence of drought, the relationship between synoptic-scale mechanisms and drought, predictability of vegetation and crop yields, stability of remote influences, data uncertainty, and the role of temperature. Development of a regional framework for cooperative work and dissemination of information and existing forecasts would speed understanding and make better use of available information.

Humans and fire: changing relations in early agricultural and built environments in the Zagros, Iran, Iraq

Fire-centred studies have recently been highlighted as powerful avenues for investigation of energy flows and relations between humans, materials, environments and other species. The aim in this paper is to evaluate this potential first by reviewing the diverse theories and methods that can be applied to investigate the ecological and social significance of anthropogenic fire, and second by applying these to new and existing data sets in archaeology. This paper examines how fire-centred approaches can inform on one of the most significant step-changes in human lifeways and inter-relations with environment and other species – the transition from mobile hunting-gathering to more sedentary agriculture in a key heartland of change, the Zagros region of Iraq and Iran, c. 12,000–8,000 BP. In the review and case studies multiple links are investigated between human fire use and environment, ecology, energy use, technology, the built environment, health, social roles and relations, cultural practices and catastrophic events

The use of remotely sensed rainfall for managing drought risk: a case study of weather index insurance in Zambia

Remotely sensed rainfall is increasingly being used to manage climate-related risk in gauge sparse regions. Applications based on such data must make maximal use of the skill of the methodology in order to avoid doing harm by providing misleading information. This is especially challenging in regions, such as Africa, which lack gauge data for validation. In this study, we show how calibrated ensembles of equally likely rainfall can be used to infer uncertainty in remotely sensed rainfall estimates, and subsequently in assessment of drought. We illustrate the methodology through a case study of weather index insurance (WII) in Zambia. Unlike traditional insurance, which compensates proven agricultural losses, WII pays out in the event that a weather index is breached. As remotely sensed rainfall is used to extend WII schemes to large numbers of farmers, it is crucial to ensure that the indices being insured are skillful representations of local environmental conditions. In our study we drive a land surface model with rainfall ensembles, in order to demonstrate how aggregation of rainfall estimates in space and time results in a clearer link with soil moisture, and hence a truer representation of agricultural drought. Although our study focuses on agricultural insurance, the methodological principles for application design are widely applicable in Africa and elsewhere.

Surface Urban Energy and Water Balance Scheme (SUEWS): development and evaluation at two UK sites

The Surface Urban Energy and Water Balance Scheme (SUEWS) is evaluated at two locations in the UK: a dense urban site in the centre of London and a residential suburban site in Swindon. Eddy covariance observations of the turbulent fluxes are used to assess model performance over a twoyear period (2011-2013). The distinct characteristics of the sites mean their surface energy exchanges differ considerably. The model suggests the largest differences can be attributed to surface cover (notably the proportion of vegetated versus impervious area) and the additional energy supplied by human activities. SUEWS performs better in summer than winter, and better at the suburban site than the dense urban site. One reason for this is the bias towards suburban summer field campaigns in observational data used to parameterise this (and other) model(s). The suitability of model parameters (such as albedo, energy use and water use) for the UK sites is considered and, where appropriate, alternative values are suggested. An alternative parameterisation for the surface conductance is implemented, which permits greater soil moisture deficits before evaporation is restricted at non-irrigated sites. Accounting for seasonal variation in the estimation of storage heat flux is necessary to obtain realistic wintertime fluxes.

The matrix-tolerance hypothesis: an empirical test with frogs in the Atlantic Forest

The matrix-tolerance hypothesis suggests that the most abundant species in the inter-habitat matrix would be less vulnerable to their habitat fragmentation. This model was tested with leaf-litter frogs in the Atlantic Forest where the fragmentation process is older and more severe than in the Amazon, where the model was first developed. Frog abundance data from the agricultural matrix, forest fragments and continuous forest localities were used. We found an expected negative correlation between the abundance of frogs in the matrix and their vulnerability to fragmentation, however, results varied with fragment size and species traits. Smaller fragments exhibited stronger matrix-vulnerability correlation than intermediate fragments, while no significant relation was observed for large fragments. Moreover, some species that avoid the matrix were not sensitive to a decrease in the patch size, and the opposite was also true, indicating significant differences with that expected from the model. Most of the species that use the matrix were forest species with aquatic larvae development, but those species do not necessarily respond to fragmentation or fragment size, and thus affect more intensively the strengthen of the expected relationship. Therefore, the main relationship expected by the matrix-tolerance hypothesis was observed in the Atlantic Forest; however we noted that the prediction of this hypothesis can be substantially affected by the size of the fragments, and by species traits. We propose that matrix-tolerance model should be broadened to become a more effective model, including other patch characteristics, particularly fragment size, and individual species traits (e. g., reproductive mode and habitat preference).

Successful carnivore identification with faecal DNA across a fragmented Amazonian landscape

The use of scat surveys to obtain DNA has been well documented in temperate areas, where DNA preservation may be more effective than in tropical forests. Samples obtained in the tropics are often exposed to high humidity, warm temperatures, frequent rain and intense sunlight, all of which can rapidly degrade DNA. Despite these potential problems, we demonstrate successful mtDNA amplification and sequencing for faeces of carnivores collected in tropical conditions and quantify how sample condition and environmental variables influence the success of PCR amplification and species identification. Additionally, the feasibility of genotyping nuclear microsatellites from jaguar (Panthera onca) faeces was investigated. From October 2007 to December 2008, 93 faecal samples were collected in the southern Brazilian Amazon. A total of eight carnivore species was successfully identified from 71% of all samples obtained. Information theoretic analysis revealed that the number of PCR attempts before a successful sequence was an important negative predictor across all three responses (success of species identification, success of species identification from the first sequence and PCR amplification success), whereas the relative importance of the other three predictors (sample condition, season and distance from forest edge) varied between the three responses. Nuclear microsatellite amplification from jaguar faeces had lower success rates (15-44%) compared with those of the mtDNA marker. Our results show that DNA obtained from faecal samples works efficiently for carnivore species identification in the Amazon forest and also shows potential for nuclear DNA analysis, thus providing a valuable tool for genetic, ecological and conservation studies.

Taxon surrogates among Amazonian mammals: Can total species richness be predicted by single orders?

Limited financial sources and the difficulty in performing complete surveys, allied to the speed of habitat fragmentation and the urgent necessity in select conservation areas, create the necessity of using some methodologies which bypass these problems. One possibility is the use of surrogate taxa that might be used as indicator of others groups richness and even total richness of an area. We investigated if the use of surrogate taxon is useful among seven mammal orders in Amazon. We tested through Pearson`s correlation (Bonferroni`s adjusted) if (1) there was a correlation between richness of total species and some order; (2) there was a significant pair wise correlation between species richness of each order; and (3) the combination of two orders would give better results as a surrogate for the total richness. The correlations found, in general, were positive. It means that the increase in the richness of an order was followed by its increase in another order, as well as in the total species richness. Only Didelphimorphia was significantly correlated with the total species richness. In the pair wise analyses only one assembly, Primates and Artiodactyla, was significantly correlated with total richness. Since indicator species are more effective within taxonomic groups (life-history characteristics are likely to be more different among than within major taxonomic groups), we suggest that an indicator group might be chosen for each one. In this case, for mammals from Amazon, it would be Didelphimorphia. (C) 2008 Elsevier Ltd. All rights reserved.

Differential effects of alpha-helical and beta-hairpin antimicrobial peptides against Acanthamoeba castellanii

In this work we evaluated the ability of different types of antimicrobial peptides to promote permeabilization and growth inhibition of Acanthamoeba castellanii trophozoites, which cause eye keratitis. We used cationic alpha-helical peptides P5 and a beta-hairpin amphipathic molecule (gomesin), of the spider Acanthoscurria gomesiana haemocytes. A. castellanii permeabilization was obtained after 1 h incubation with micromolar concentrations of both types of peptides. While permeabilization induced by gomesin increased with longer incubations, P5 permeabilization did not increase with time and occurred at doses that are more toxic for SIRC cells, P5, however, at doses below the critical dose used to kill rabbit corneal cells was quite effective in promoting growth inhibition. Similarly, P5 was more effective when serine protease inhibitor was added simultaneously to the permeabilization assay. High performance chromatography followed by mass spectrometry analysis confirmed that, in contrast to gomesin, P5 is hydrolysed by A. castellanii culture supernatants. We conclude that the use of antimicrobial peptides to treat A. castellanii infections requires the search of more specific peptides that are resistant to proteolysis.

Enhancement of Th1 Lung Immunity Induced by Recombinant Mycobacterium bovis Bacillus Calmette-Guerin Attenuates Airway Allergic Disease

Mycobacterium bovis Bacillus Calmette-Guerin (BCG) has been shown to down-regulate experimental allergic asthma, a finding that reinforced the hygiene hypothesis. We have previously found that recombinant BCG (rBCG) strain that express the genetically detoxified Si subunit of pertussis toxin (rBCG-S1PT) exerts an adjuvant effect that enhances Th1 responses against BCG proteins. Here we investigated the effect of this rBCG-S1PT on the classical ovalbumin-induced mouse model of allergic lung disease. We found that rBCG-S1PT was more effective than wild-type BCG in preventing Th2-mediated allergic immune responses. The inhibition of allergic lung disease was not associated with increased concentration of suppressive cytokines or with an increased number of pulmonary regulatory T cells but was positively correlated with the increase in IFN-gamma-producing T cells and T-bet expression in the lung. In addition, an IL-12-dependent mechanism appeared to be important to the inhibition of lung allergic disease. The inhibition of allergic inflammation was found to be restricted to the lung because when allergen challenge was given by the intraperitoneal route, rBCG-S1PT administration failed to inhibit peritoneal allergic inflammation and type 2 cytokine production. Our work offers a nonclassical interpretation for the hygiene hypothesis indicating that attenuation of lung allergy by rBCG could be due to the enhancement of local lung Th1 immunity induced by rBCG-S1PT. Moreover, it highlights the possible use of rBCG strains as multipurpose immunomodulators by inducing specific immunity against microbial products while protecting against allergic asthma.